Recent instrumental developments in mass spectrometry, such as electrospray ionization (ESI) and matrix assisted laser desorption time-of- flight mass spectrometry (MALDI TOF), have enabled the mass spectrometrist to investigate biological species with significantly higher average molecular weight than previously possible. The combination of these techniques with chemical processing of large biological species such as proteins now enables the use of mass spectrometry to determine a wide range of problems within the realm of structural biology. Within the past year, we have begun to address several issues in structural biochemistry. The goal of one project, in collaboration with Dr J. Hoeg, MDB/NHLBI/NIH, and W. Weinmann/ Prof. M. Przybylski, Univ. Konstanz, is to determine the sites of palmitoylation analon of phosphorylation of apolipoprotein A-1 secreted by the human hepatoma cell line Hep G2. A second issue is the isolation/structure determination of proteins that have been conjugated with xenobiotics through exposure. The first model to be investigated in this system is the hemoglobin- isoprene adduct isolated from the blood of mice exposed to isoprene. The third issue being addressed is the application of MS techniques to the investigation of enzyme-substrate/receptor-substrate interactions.